Apnea of prematurity is defined as respiratory pauses > 20 sec or pauses < 20 sec that are associated with bradycardia (< 80 beats/min), central cyanosis, and/or O2 saturation < 85% in neonates born at < 37 wk gestation and with no underlying disorders causing apnea. Cause may be CNS immaturity (central) or airway obstruction. Diagnosis is by multichannel respiratory monitoring. Treatment is with respiratory stimulants for central apnea and head positioning for obstructive apnea. Prognosis is excellent; apnea resolves in most neonates by 37 wk.

About 25% of preterm infants (see Premature Infant ) have apnea of prematurity, which usually begins 2 to 3 days after birth and only rarely on the first day. Apnea that develops > 14 days after birth in an otherwise healthy infant signifies a serious illness other than apnea of prematurity (eg, sepsis [see Neonatal Sepsis]). Risk increases with earlier gestational age.

Pathophysiology

Apnea of prematurity is a developmental disorder caused by immaturity of neurologic and/or mechanical function of the respiratory system. Apnea may be characterized as

Central

Obstructive

A mixed pattern (most common)

Central apnea is caused by immature medullary respiratory control centers. The specific pathophysiology is not understood completely but appears to involve a number of factors, including abnormal responses to hypoxia and hypercapnia.

All types of apnea can cause hypoxemia, cyanosis, and bradycardia if the apnea is prolonged. Among infants dying of SIDS (see Sudden Infant Death Syndrome (SIDS)), 18% have a history of prematurity, but apnea of prematurity is not a precursor to SIDS.

Periodic breathing is repeated cycles of 5 to 20 sec of normal breathing alternating with brief (< 20 sec) periods of apnea. This phenomenon is common among premature infants and has little or no clinical significance.

Diagnosis

Although frequently attributable to immature respiratory control mechanisms, apnea in premature infants can be sign of infectious, metabolic, thermoregulatory, respiratory, cardiac, or CNS dysfunction. Thorough history, physical assessment, and, when necessary, testing should be done before accepting prematurity as the cause of apnea. Gastroesophageal reflux disease (GERD—see Gastroesophageal Reflux in Infants ) is no longer thought to cause apnea in preterm infants, so the presence of GERD should not be considered an explanation for apneic episodes.

Diagnosis of apnea usually is made by visual observation or by use of impedance-type cardiorespiratory monitors used continuously during assessment and ongoing care of preterm infants. Multichannel recordings of multiple physiologic parameters (eg, chest wall movement, airflow, O2 saturation, heart rate, brain electric activity) taken for up to 24 h can be used as adjuncts for diagnosis and planning and monitoring treatment. However, these more advanced tests are not necessary for discharge planning.

Prognosis

Most preterm infants stop having apneic spells by the time they reach about 37 wk gestation. Apnea may continue for weeks in infants born at extremely early gestational ages (eg, 23 to 27 wk). Death is rare.

Treatment

Stimulation

Treatment of underlying disorder

Respiratory stimulants (eg, caffeine)

When apnea is noted, either by observation or monitor alarm, infants are stimulated, which may be all that is required; if breathing does not resume, bag-valve-mask or mouth-to-mouth-and-nose ventilation is provided (see Airway Establishment and Control : Airway and Respiratory Devices). For infants at home, the physician is contacted if apnea occurs but ceases after stimulation; if intervention beyond stimulation is required, the infant should be rehospitalized and evaluated.

Frequent or severe episodes should be quickly and thoroughly evaluated, and identifiable causes should be treated. If no infectious or other treatable underlying disorder is found, respiratory stimulants are indicated for treatment of frequent or severe episodes, characterized by hypoxemia, cyanosis, bradycardia, or a combination. Caffeine is the safest and most commonly used respiratory stimulant drug. It can be given as caffeine base (loading dose 10 mg/kg followed by a maintenance dose of 2.5 mg/kg po q 24 h) or caffeine citrate, a caffeine salt that is 50% caffeine (loading dose 20 mg/kg followed by a maintenance dose of 5 to 10 mg/kg q 24 h). Caffeine is preferred because of ease of administration, fewer adverse effects, larger therapeutic window, and less need to monitor drug levels. Treatment continues until the infant is 34 to 35 wk gestation and free from apnea requiring physical intervention for at least 5 to 7 days. Monitoring continues until the infant is free of apnea requiring intervention for 5 to 10 days.

Prevention

Home monitoring

Hospitalized high-risk infants who have not had clinically significant cardiopulmonary events (eg, apnea > 20 sec, apnea accompanied by central cyanosis, apnea associated with heart rate < 80 for > 5 sec) during 3 to 10 days of continuous cardiorespiratory monitoring can be discharged home safely without a monitor. Sometimes a home cardiorespiratory monitor and/or oral caffeine may be prescribed to shorten the hospital stay for infants who are otherwise ready for discharge but are still having cardiopulmonary events that reverse without intervention. However, infants who have events that require intervention, including stimulation, are not discharged from the hospital.

Pearls & Pitfalls

Home cardiorespiratory monitors have not been shown to reduce the incidence of SIDS or ALTEs.

Positioning

Infants should always be placed on their back to sleep. The infant’s head should be kept in the midline, and the neck should be kept in the neutral position or slightly extended to prevent upper airway obstruction. All premature infants, especially those with apnea of prematurity, are at risk of apnea, bradycardia, and O2 desaturation while in a car seat and should undergo a car seat challenge test before discharge.

Key Points

Apnea of prematurity is caused by immaturity of neurologic and/or mechanical function of the respiratory system.

Merck and the Merck Manuals

Merck & Co., Inc., Kenilworth, NJ, USA is a global healthcare leader working to help the world be well. From developing new therapies that treat and prevent disease to helping people in need, we are committed to improving health and well-being around the world. The Merck Manual was first published in 1899 as a service to the community. The legacy of this great resource continues as the Merck Manual in the US and Canada and the MSD Manual outside of North America. Learn more about our commitment to Global Medical Knowledge.